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      Engineered hydrogels for mechanobiology

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          Abstract

          Cells’ local mechanical environment can be as important in guiding cellular responses as many well-characterized biochemical cues. Hydrogels that mimic the native extracellular matrix can provide these mechanical cues to encapsulated cells, allowing for the study of their impact on cellular behaviours. Moreover, by harnessing cellular responses to mechanical cues, hydrogels can be used to create tissues in vitro for regenerative medicine applications and for disease modelling. This Primer outlines the importance and challenges of creating hydrogels that mimic the mechanical and biological properties of the native extracellular matrix. The design of hydrogels for mechanobiology studies is discussed, including appropriate choice of cross-linking chemistry and strategies to tailor hydrogel mechanical cues. Techniques for characterizing hydrogels are explained, highlighting methods used to analyze cell behaviour. Example applications for studying fundamental mechanobiological processes and regenerative therapies are provided, along with a discussion of the limitations of hydrogels as mimetics of the native extracellular matrix. The article ends with an outlook for the field, focusing on emerging technologies that will enable new insights into mechanobiology and its role in tissue homeostasis and disease.

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          Most cited references203

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          NCBI GEO: archive for functional genomics data sets—update

          The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) is an international public repository for high-throughput microarray and next-generation sequence functional genomic data sets submitted by the research community. The resource supports archiving of raw data, processed data and metadata which are indexed, cross-linked and searchable. All data are freely available for download in a variety of formats. GEO also provides several web-based tools and strategies to assist users to query, analyse and visualize data. This article reports current status and recent database developments, including the release of GEO2R, an R-based web application that helps users analyse GEO data.
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            Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

            In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
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              Matrix elasticity directs stem cell lineage specification.

              Microenvironments appear important in stem cell lineage specification but can be difficult to adequately characterize or control with soft tissues. Naive mesenchymal stem cells (MSCs) are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity. Soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. During the initial week in culture, reprogramming of these lineages is possible with addition of soluble induction factors, but after several weeks in culture, the cells commit to the lineage specified by matrix elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types. Inhibition of nonmuscle myosin II blocks all elasticity-directed lineage specification-without strongly perturbing many other aspects of cell function and shape. The results have significant implications for understanding physical effects of the in vivo microenvironment and also for therapeutic uses of stem cells.
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                Author and article information

                Contributors
                Journal
                101778010
                Nat Rev Methods Primers
                Nat Rev Methods Primers
                Nature reviews. Methods primers
                2662-8449
                15 December 2022
                12 July 2023
                17 July 2023
                : 2
                : 98
                Affiliations
                [1 ]Fraunhofer Institute for Cell Therapy and Immunology and Fraunhofer Cluster of Excellence for Immune-Mediated Disease, Leipzig, Germany
                [2 ]Department of Chemical and Biomolecular Engineering, University of Delaware, DE, USA
                [3 ]Department of Mechanical Engineering, Stanford University, CA, USA
                [4 ]Institute for Complex Molecular Systems, Department of Biomedical Engineering, Laboratory of Chemical Biology, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
                [5 ]Department of Material Science and Engineering, University of Delaware, DE, USA
                [6 ]University Hospital Balgrist and ETH Zurich, Zurich, Switzerland
                [7 ]Centre for Craniofacial and Regenerative Biology, King’s College London, London SE1 9RT, UK
                Article
                EMS179193
                10.1038/s43586-022-00179-7
                7614763
                37461429
                20109c33-9f02-4160-a66f-20d246474991

                This work is licensed under a CC BY 4.0 International license.

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